7-99838116-A-G

Variant names:

• chr7-99838116-A-G
• rs642761
• NM_057095.3:c.166-1004A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_057095.3(CYP3A43):​c.166-1004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,178 control chromosomes in the GnomAD database, including 9,646 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (9646 hom., cov: 32)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869
• Publications: 3 publications found

Genes affected

CYP3A43 (HGNC:17450): (cytochrome P450 family 3 subfamily A member 43) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein has a low level of testosterone hydroxylase activity, and may play a role in aging mechanisms and cancer progression. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057095.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A43	NM_057095.3	MANE Select	c.166-1004A>G		intron	N/A	NP_476436.1	Q9HB55-1
	CYP3A43	NM_022820.5		c.166-1004A>G		intron	N/A	NP_073731.1	Q9HB55-2
	CYP3A43	NM_057096.4		c.166-1004A>G		intron	N/A	NP_476437.1	Q9HB55-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A43	ENST00000354829.7	TSL:1 MANE Select	c.166-1004A>G		intron	N/A	ENSP00000346887.3	Q9HB55-1
	CYP3A43	ENST00000222382.5	TSL:1	c.166-1004A>G		intron	N/A	ENSP00000222382.5	Q9HB55-2
	CYP3A43	ENST00000312017.9	TSL:1	c.166-1004A>G		intron	N/A	ENSP00000312110.5	Q9HB55-3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36260 AN: 152062 Hom.: 9616 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.204

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36341 AN: 152178 Hom.: 9646 Cov.: 32 AF XY: 0.232 AC XY: 17261 AN XY: 74396

African (AFR) AF: 0.661 AC: 27444 AN: 41488

American (AMR) AF: 0.144 AC: 2209 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.0769 AC: 371 AN: 4824

European-Finnish (FIN) AF: 0.0582 AC: 617 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0706 AC: 4797 AN: 67992

Other (OTH) AF: 0.203 AC: 428 AN: 2110

Alfa AF: 0.117 Hom.: 1294

Bravo AF: 0.264

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs642761; hg19: chr7-99435739;